1 Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with the morphine-induced allodynia and the nociceptin-evoked hyperalgesia. 2 Nociceptin-induced allodynia was evoked by the ®rst stimulus 5 min after i.t. injection, reached a maximum at 10 min, and continued for a 50 min experimental period. Dose-dependency of the allodynia showed a bell-shaped pattern from 50 pg to 5 ng kg 71 , and the maximum e ect was observed at 2.5 ng kg 71 . 3 Morphine-induced allodynia reached the maximum e ect at 15 min and declined progressively until cessation by 40 ± 50 min. The dose-response curve showed a bell-shaped pattern, similar to that induced by nociceptin, with a maximum e ect at 0.5 mg kg 71 , ®ve orders of magnitude higher than that of nociceptin. 4 The allodynia evoked by nociceptin and morphine were dose-dependently blocked by glycine, D(7)-2-amino-5-phosphonovaleric acid (D-AP5, an N-methyl-D-aspartate (NMDA) receptor antagonist), g-Dglutamylaminomethyl sulphonic acid (GAMS, a non-NMDA receptor antagonist) and methylene blue (a soluble guanylate cyclase inhibitor), but were not a ected by muscimol (a g-aminobutyric acid A (GABA A ) receptor agonist) and baclofen (a GABA B receptor agonist). 5 Morphine did not inhibit forskolin-stimulated cyclicAMP formation in cultured cells expressing the nociceptin receptor. 6 Nociceptin-induced hyperalgesia was evoked 10 ± 15 min after i.t. injection. Nociceptin produced a monophasic hyperalgesic action over a wide range of doses from 5 fg to 50 ng kg 71 . The nociceptininduced hyperalgesia was blocked by glycine only among the agents examined. 7 None of the pain responses evoked by nociceptin and morphine were blocked by naloxone. 8 These results demonstrate that, whereas the mechanisms of the nociceptin-induced allodynia and hyperalgesia are evidently distinct, they involve a common neurochemical event beginning with the disinhibition of the inhibitory glycinergic response. Morphine may induce allodynia through a pathway common to nociceptin, but the nociceptin receptor does not mediate the action of high doses of morphine.
These results demonstrate that both strychnine- and bicuculline-evoked allodynia were mediated through pathways that include the glutamate receptor and nitric oxide systems but in a different manner. the current study suggests that GABA and glycine may modulate responses to an innocuous tactile stimulus as inhibitory neurotransmitters at presynaptic and postsynaptic sites in the spinal cord, respectively.
HighlightsThe combination of embolization of the splenic artery and continuous epinephrine infusion to reduce the spleen volume was highly effective.New technique of laparosopic splenolectomy for massive splenomegaly.Spleen volume started to decrease immediately after the onset of intravenous infusion of low-dose epinephrine.
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